Malaria's Achilles' heel revealed?

Parasite requires a single receptor to invade human red blood cells

Video resource: Malaria's Achilles's heel revealed?

Researchers have today (9 November 2011) revealed a key discovery in understanding how the most deadly species of
malaria parasite, Plasmodium falciparum, invades human red blood cells. Using a technique developed at the
Wellcome Trust Sanger Institute, they have found that the parasite relies on a single receptor on the red blood cell's
surface to invade, offering an exciting new focus for vaccine development.

Malaria kills approximately one million people every year, mostly children under the age of five in sub-Saharan Africa.
Currently no licensed vaccine is available.

The blood stage of Plasmodium's lifecycle begins when the parasite invades human red blood cells, and it is
this stage that is responsible for the symptoms and mortality associated with malaria. Researchers have tried for many
years to develop a vaccine to prevent the parasite gaining entry into our red blood cells, but so far they have been
unsuccessful. One of the challenges is that the parasite is adaptable - although several red blood cell receptors had
been previously identified, none was shown to be essential: when entry through one receptor is prevented, the parasite
is able to switch to another. This new research has found a single receptor that is absolutely required by the parasite
to invade.

"Our findings were unexpected and have completely changed the way in which we view the invasion
process," says Dr Gavin Wright, senior co-author from the Wellcome Trust Sanger Institute. "Our research seems to have revealed an Achilles' heel in the way the parasite invades our red blood cells. It
is rewarding to see how our techniques can be used to answer important biological problems and lay the foundations for
new therapies."

" By identifying a single receptor that appears to be essential for parasites to invade human red blood cells, we
have also identified an obvious and very exciting focus for vaccine development. The hope is that this work will
lead towards an effective vaccine based around the parasite protein. "

Dr Julian Rayner

The interaction between the parasite protein and the host receptor was discovered using a technique called AVEXIS
(Avidity-based Extracellular Interaction Screen). This technology, created by Dr Gavin Wright's team at the Sanger
Institute, was specifically designed to detect extracellular receptor-ligand interactions of this type.

As well as identifying the interaction, the researchers demonstrated that disrupting this interaction completely
blocked the parasite from gaining entry into the red blood cell. Importantly, this was true across all parasite strains
tested, making it appear that the receptor is a universal entry pathway. It is hoped that the parasite's dependency on
this one protein can now be exploited to develop new and effective vaccines.

"By identifying a single receptor that appears to be essential for parasites to invade human red
blood cells, we have also identified an obvious and very exciting focus for vaccine development," says Dr Julian
Rayner, senior co-author from the Sanger Institute. "The hope is that this work will lead towards
an effective vaccine based around the parasite protein."

Vaccinating against malaria will be the most cost-effective and simplest way to protect populations against the
disease. However, for such an approach to work at the population scale, the vaccine needs to be highly effective so
that the vast majority of those vaccinated are immune to the disease. This new research identifies an exciting
candidate for such a vaccine.

"Recent reports of some positive results from ongoing malaria vaccine trials in Africa are
encouraging, but in the future more effective vaccines will be needed if malaria is ever to be eradicated," says
Professor Adrian Hill, Wellcome Trust Senior Investigator at the Jenner Institute, University of Oxford. "The discovery of a single receptor that can be targeted to stop the parasite infecting red blood cells offers
the hope of a far more effective solution."

Notes to Editors

Publication details

Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum.

The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.

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The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.